1. Field of the Invention
The present invention pertains to a non-primate vitreal replacement process that quantitates the inflammatory response to viscoelastic agents or solutions.
2. Description of the Prior Art
The owl monkey (Aotus trivigatus) was used as a process for measuring the inflammatory response of intravitreous hyaluronic acid injections. The owl monkey was selected because it was found that when full grown, this new world monkey had a liquid vitreous. [Balazs, Laurent, DeRoche and Bunney,(1959) Studies on the structure of the vitreous body VIII. Comparative Biochemistry. Arch. Blochem Biophys.81,464-79.] The presence of a liquid rather than a gel vitreous was a prerequisite for these tests. The exchange of viscous liquid vitreous with a biopolymer solution had to be achieved with minimal surgical trauma in order to evaluate the tolerance of the vitreous substance used. The owl monkey vitreous test was consequently developed as an extremely sensitive method to evaluate the inflammatory reaction in the vitreous after the injection of viscoelastic solutions. [Balazs, E. A. and Sweeney, D. B. (1966) Replacement of the vitreous body of monkeys with reconstituted vitreous and hyaluronic acid. in Modern Problems in Ophthalmology (Surgery of retinal vascular diseases and prophylactic treatment of retinal detachment, Amersfoort 1963 (ed. Streiff, E. B.). Vol 4 pp. 230-32.][S. Karger, Basel, New York. Balazs, E. A. and Sweeney, D. (1966). The injection of hyaluronic acid and reconstituted vitreous into the vitreous cavity. In New and Controversial Aspects of Retinal Detachment (Ed. McPherson) pp. 371-6. Harper and Row, New York.] the liquid vitreous of the owl monkey can be easily replaced without mechanical damage to the retina and lens. The minimal operational trauma permits a very accurate and sensitive evaluation of the tolerance of the vitreal implant.
These studies were aimed at establishing whether or not a highly purified special fraction of sodium hyaluronate when implanted into the vitreous, causes any immediate inflammatory reaction in the eye. U.S. Pat. No. 4,141,973 to Balazs describes a modified owl monkey test to test the inflammatory reaction of ultrapure hyaluronic acid.
Another primate that has been used to test the inflammatory reaction of ultrapure hyaluronic acid is the rhesus monkey. Although the total volume of the vitreous of the adult rhesus eye is approximately 24% larger than the owl monkey eye, the volume of the liquid vitreous is smaller (0.8 to 1.2 ml) in the rhesus than the owl monkey eye (1.8-2.2 ml). In the rhesus monkey, only 0.5 ml of vitreous can be removed and replaced. By reducing the volume of vitreous removed and replaced, the incidence of eyeball collapse is greatly reduced, and therefore, there is less traumatic injury to the blood aqueous barrier. The rhesus monkey has been shown to have similar inflammatory reactions as the owl monkey, after vitreal injection of Healon.RTM.. The rhesus monkey can also be used as an extremely sensitive system for detecting small amounts of inflammatory agents. (Denlinger, J. L. and Balazs, E. A., Replacement of the Liquid Vitreous with Sodium Hyaluronate in Monkeys. Experimental Eye Research (1980) 31, 81-99.)
The present invention overcomes the disadvantages of the prior art by providing a process for quantifying the inflammatory response to viscoelastic agents or solutions in New Zealand White rabbit, which is readily available.